Previous HGNC Symbols for KCNQ1 Gene

Previous GeneCards Identifiers for KCNQ1 Gene

Summaries for KCNQ1 Gene

Entrez Gene Summary for KCNQ1 Gene

This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

UniProtKB/Swiss-Prot for KCNQ1 Gene

Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:10646604). Associates with KCNE beta subunits that modulates current kinetics (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568).

Isoform 2: Non-functional alone but modulatory when coexpressed with the full-length isoform 1.

Tocris Summary for KCNQ1 Gene

Voltage-gated potassium channels (KV) belong to the 6-TM family of potassium channel that also comprises the Ca2+-activated Slo (actually 7-TM) and the Ca2+-activated SK subfamilies. The alpha-subunits contain a single pore-forming region and combine to form tetramers.

Mutagenesis experiments were carried out by expressing in Xenopus oocytes or COS-7 cells KCNQ1 mutants either individually (homomultimers) or in combination with both wild-type KCNQ1 (mut/wt homomultimers) and minK (heteromultimers).

Post-translational modifications for KCNQ1 Gene

Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9.

Ubiquitinated by NEDD4L; promotes internalization (PubMed:22024150). The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A (PubMed:23529131).

Function for KCNQ1 Gene

Products:

Molecular function for KCNQ1 Gene

GENATLAS Biochemistry:

potassium voltage-gated channel,KQT subfamily,member 1,Drosophila shaker-related subfamily,associating with KCNE1 to form the slow delayed-rectifier IKS channel,paternally imprinted (centromeric imprinting domain at 11p15,containing TSSC3,TSSC5 and KCNQ1) in a tissue specific pattern with six isoforms,predominantly expressed in heart,also in stria vascularis that secretes the endolymph,not expressed in skeletal muscle,may be disrupted in (some) Beckwith-Wiedemann syndromes,see also LIT1

Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:10646604). Associates with KCNE beta subunits that modulates current kinetics (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568).

Localization for KCNQ1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNQ1 Gene

Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane. Early endosome. Membrane raft. Endoplasmic reticulum. Basolateral cell membrane. Note=Colocalized with KCNE3 at the plasma membrane (PubMed:10646604). Upon 17beta-oestradiol treatment, colocalizes with RAB5A at early endosome (PubMed:23529131). Heterotetramer with KCNQ5 is highly retained at the endoplasmic reticulum and is localized outside of lipid raft microdomains (PubMed:24855057). During the early stages of epithelial cell polarization induced by the calcium switch it removed from plasma membrane to the endoplasmic reticulum where it retained and it is redistributed to the basolateral cell surface in a PI3K-dependent manner at a later stage (PubMed:21228319). {ECO:0000269 PubMed:10646604, ECO:0000269 PubMed:21228319, ECO:0000269 PubMed:23529131, ECO:0000269 PubMed:24855057}.

UniProtKB/Swiss-Prot

Atrial fibrillation, familial, 3 (ATFB3) [MIM:607554]: An autosomal dominant form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269 PubMed:12522251}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:18711366, ECO:0000269 PubMed:18711367, ECO:0000269 PubMed:24390345}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Short QT syndrome 2 (SQT2) [MIM:609621]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. {ECO:0000269 PubMed:15159330}. Note=The disease is caused by mutations affecting the gene represented in this entry.

A single nucleotide polymorphism in KCNQ1 is associated with susceptibility to diabetic nephropathy in japanese subjects with type 2 diabetes.(PMID: 20056949)Ohshige T. … Maeda S.(Diabetes Care 2010)3224664